Pazopanib-d6

Pazopanib-d₆ is intended for use as an internal standard for the quantification of pazopanib by GC- or LC-MS. Pazopanib is a multi-kinase inhibitor that inhibits the VEGF receptors VEGFR1, VEGFR2, and VEGFR3 (IC₅₀s = 10, 30, and 47 nM, respectively, in a cell-free enzyme assay).¹ It also inhibits PDGFRα, PDGFRβ, and c-Kit (IC₅₀s = 71, 84, and 74 nM, respectively, in a cell-free enzyme assay) as well as additional receptor tyrosine kinases. Pazopanib inhibits upregulation of the surface adhesion proteins ICAM-1 and VCAM-1 induced by VEGF in multiple myeloma cells cocultured with human umbilical vein endothelial cells (HUVECs) and decreases multiple myeloma cell adhesion to HUVECs.² It also inhibits proliferation of multiple myeloma cells cocultured with HUVECs. Pazopanib (30 and 100 mg/kg) reduces tumor growth, induces apoptosis, decreases angiogenesis, and increases survival in a multiple myeloma mouse xenograft model. Formulations containing pazopanib have been used in the treatment of cancer.

1. Kumar, R., Knick, V.B., Rudolph, S.K., et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity Mol. Cancer Ther. 6(7),2012-2021(2007).
2. Podar, K., Tonon, G., Satler, M., et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma Proc. Natl. Acad. Sci. USA 103(5),19478-19483(2006).